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WO1996035435A1 - Compositions contenant du bismuth, pour la prevention et le traitement de troubles gastro-intestinaux - Google Patents

Compositions contenant du bismuth, pour la prevention et le traitement de troubles gastro-intestinaux Download PDF

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Publication number
WO1996035435A1
WO1996035435A1 PCT/US1996/006488 US9606488W WO9635435A1 WO 1996035435 A1 WO1996035435 A1 WO 1996035435A1 US 9606488 W US9606488 W US 9606488W WO 9635435 A1 WO9635435 A1 WO 9635435A1
Authority
WO
WIPO (PCT)
Prior art keywords
bismuth
milligrams
per day
subject
parasitic protozoa
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1996/006488
Other languages
English (en)
Inventor
Jamesina Anne Fitzgerald
Joshua Lederberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Procter and Gamble Co filed Critical Procter and Gamble Co
Priority to JP8534217A priority Critical patent/JPH11504939A/ja
Priority to AU57335/96A priority patent/AU5733596A/en
Priority to EP96915593A priority patent/EP0830134A1/fr
Publication of WO1996035435A1 publication Critical patent/WO1996035435A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/245—Bismuth; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/29—Antimony or bismuth compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • an object of the present invention is to provide a safe and effective method of preventing and/or treating gastrointestinal disorders caused or mediated by parasitic protozoa.
  • a further object of the invention is to provide such a method comprising the administration of bismuth.
  • the present invention relates to a method for treatment of a human or lower animal subject having a gastrointestinal disorder caused or mediated by one or more parasitic protozoa comprising administering to the subject from about 50 milligrams to about 5000 milligrams of bismuth, per day, for from about 1 to 56 days.
  • the present invention also relates to a method for prevention in a human or lower animal of a gastrointestinal disorder caused or mediated by one or more parasitic protozoa comprising administering to the subject from about 50 milligrams to about 5000 milligrams of bismuth, per day, for from about 1 to 28 days.
  • the methods of the present invention comprise the prevention and/or treatment of gastrointestinal disorder caused or mediated by one or more parasitic protozoa. Such gastrointestinal disorders are prevented and/or treated by the administration of bismuth.
  • the components of the present invention are more fully defined below.
  • gastrointestinal disorder encompasses any infection, disease or other disorder of body, typically of the upper and/or lower gastrointestinal tract, caused or mediated by one or more parasitic protozoa.
  • disorders include one or more of the following conditions: diarrhea, abdominal pain and/or cramping, flatulence, nausea, abdominal distention, fever, constipation, blood, mucus and/or pus present in feces, vomiting, gastroenteritis, weight loss, anorexia, malaise, and any other condition commonly associated with infection by parasitic protozoa.
  • gastrointestinal disorder also includes any condition commonly associated with protozoa infection in immunocompromised subjects and children, including but not limited to, acute diarrhea, dehydration, electrolyte imbalance, colitis, and fatal necrosis of the intestine.
  • Parasitic Protozoa any condition commonly associated with protozoa infection in immunocompromised subjects and children, including but not limited to, acute diarrhea, dehydration, electrolyte imbalance, colitis, and fatal necrosis of the intestine.
  • Protozoa are unicellular, eucaryotic organisms which contain a nucleus, or nuclei, and cytoplasm. Four groups of Protozoa contain parasites which are contemplated in the present invention. These organisms are fully described in Zinsser Microbiology. 20th Edition, 1163- 1173, (1992) and T. L. Kuhls, M.D., "Protozoal Infections of the Intestinal Tract in Children", Advances In Pediatric Infectious Diseases, vol. 8, 177- 202, (1993), both of which are incorporated herein by reference.
  • parasitic protozoa refers to Protozoa of the phlya Sarcomastigophora such as Entamoeba, Giardia, Dientamoeba, and Blastocystis; Ciliophora such as Balantidium; Apicomplexa such as Isospora and Cryptospo dium; and Microspora such as Enterocytozoon.
  • Preferred parasitic protozoa are Entamoeba, Cryptospo ⁇ dium, Giardia, Isospora, and combinations thereof. Most preferred parasitic protozoa are Entamoeba, Cryptospo ⁇ dium, Giardia, and combinations thereof.
  • Diagnosis of gastrointestinal disorders caused or mediated by parasitic protozoa may be accomplished by any method commonly used in the medical community. Such methods are fully described in Zinsser Microbiology, and T.L. Kuhls, M.D. "Protozoal Infections of the Intestinal Tract in Children", as referenced above. Bismuth
  • the methods of treatment and/or prevention in the present invention involve administration of bismuth.
  • the quantity of bismuth is by weight of elemental bismuth.
  • bismuth may be administered in an amount of from about 50 milligrams to about 5000 milligrams, and preferably from about 50 milligrams to about 2500 milligrams, per day, for from about 1 to about 56 days, preferably for from about 2 to about 28 days, and most preferably for from about 7 to about 21 days.
  • bismuth may be administered in an amount of from about 50 milligrams to about 5000 milligrams, and preferably from about 50 milligrams to about 2500 milligrams, per day, for from about 1 to about 21 days, and preferably for from about 1 to about 14 days.
  • bismuth may be administered prior to potential exposure to parasitic protozoa.
  • Such administration of bismuth may vary depending on the likelihood of parasitic protozoa exposure and condition of the subject and may be commenced at any time deemed beneficial by the medical community including from about 1 to about 7 days, from about 2 to about 5 days, and from about 3 to about 4 days, prior to potential exposure.
  • bismuth may be in the form of a pharmaceutically-acceptable salt or may be in the form of an organic complex which contains bismuth as an active ingredient.
  • organic complexes include 2,2'-spirobi[1,3,2-benzodoxabismole].
  • bismuth is administered in the present methods as a pharmaceutically- acceptable salt.
  • Such bismuth salts include bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof.
  • Bismuth citrate, bismuth subcitrate, tripotassium dicitrato bismuthate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof are preferred bismuth salts for use in this invention.
  • the bismuth useful herein may be administered alone, or in combination with other pharmaceutically-acceptable components in a bismuth-containing composition.
  • a variety of such compositions containing bismuth salts are commercially available.
  • compositions include DeNol, containing tripotassium dicitrato bismuthate (by Brocades); Bislumina, containing bismuth aluminate (by Mazuelos); Roter, containing bismuth subnitrate (by Roterpharma); Devrom®, containing bismuth subgallate (by The Parthenon Co., Inc.); and Pepto-Bismol®, containing bismuth subsalicylate (by The Procter & Gamble Company).
  • administering refers to any method which, in sound medical practice delivers the compounds or compositions used in this invention to the subject to be treated in such a manner so as to be effective in the treatment of the gastrointestinal disorder.
  • the bismuth is administered orally.
  • a human subject, suffering from severe diarrhea, is treated by a method of the present invention.
  • Fecal samples are taken from the subject and analyzed for the presence of intestinal parasites, including organism eggs, cysts, sporozoites, etc.
  • Clinical parasitology specimens reveal the presence of Cryptospo ⁇ dium parvum.
  • the subject is then treated by administering a composition containing bismuth subsalicylate, sold by The Procter & Gamble Company under the name "Pepto-Bismol®".
  • the composition in liquid form, is administered four times daily in equal doses delivering approximately 2500 milligrams of bismuth per day, for 21 days. Thereafter, fecal samples from the subject are analyzed again, finding no trace of parasitic infection.
  • a three-year-old child with diabetes and in a day care center is suffering from chronic diarrhea, and abdominal distention.
  • Analysis of fecal specimens shows the presence of Giardia lamblia.
  • the infection is diagnosed and treated by orally administering approximately 400 milligrams of bismuth in the form of bismuth subcitrate ("DeNol", sold by Brocades), in four equal doses daily, for about 28 days. Thereafter, fecal samples from the subject are analyzed again, finding no trace of parasitic infection.
  • a Peace Corps volunteer preparing to travel to a developing country with sub-standard sanitation and water purification systems has a fecal sample clinically analyzed for the presence of Giardia lamblia, Cryptospo ⁇ dium parvum, and Entamoeba histolytica. Clinical results show no evidence of the parasites.
  • the subject is given approximately 1200 milligrams of bismuth, (administered as bismuth subsalicylate in the composition Pepto-Bismol®, sold by The Procter & Gamble Company), in four equal doses daily, for about 21 days.
  • the subject Upon return to the U.S., approximately 30 days after the initial clinical analysis, the subject remains asymptomatic. Fecal samples from the subject are analyzed and no evidence of parasitic infection is found.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des procédés pour la prévention et le traitement de troubles gastro-intestinaux provoqués ou transmis par un ou plusieurs protozoaires parasites chez l'homme ou chez l'animal et consistant à administrer du bismuth au sujet.
PCT/US1996/006488 1995-05-09 1996-05-08 Compositions contenant du bismuth, pour la prevention et le traitement de troubles gastro-intestinaux Ceased WO1996035435A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP8534217A JPH11504939A (ja) 1995-05-09 1996-05-08 胃腸障害の治療及び予防用のビスマス含有組成物
AU57335/96A AU5733596A (en) 1995-05-09 1996-05-08 Compositions containing bismuth, for the treatment and preve ntion of gastrointestinal disorders
EP96915593A EP0830134A1 (fr) 1995-05-09 1996-05-08 Compositions contenant du bismuth, pour la prevention et le traitement de troubles gastro-intestinaux

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US43785595A 1995-05-09 1995-05-09
US08/437,855 1995-05-09

Publications (1)

Publication Number Publication Date
WO1996035435A1 true WO1996035435A1 (fr) 1996-11-14

Family

ID=23738205

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/006488 Ceased WO1996035435A1 (fr) 1995-05-09 1996-05-08 Compositions contenant du bismuth, pour la prevention et le traitement de troubles gastro-intestinaux

Country Status (5)

Country Link
EP (1) EP0830134A1 (fr)
JP (1) JPH11504939A (fr)
AU (1) AU5733596A (fr)
CA (1) CA2219771A1 (fr)
WO (1) WO1996035435A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7300667B1 (en) 1999-05-27 2007-11-27 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract
US7364749B1 (en) 1999-05-27 2008-04-29 Euro-Celtique, S.A. Preparations for the application of anti-infective and/or anti-inflammatory agents

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE654814A (fr) * 1963-10-26 1965-02-15
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane
US4940695A (en) * 1987-12-10 1990-07-10 The Procter & Gamble Company Bismuth-containing pharmaceutical compositions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE654814A (fr) * 1963-10-26 1965-02-15
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane
US4940695A (en) * 1987-12-10 1990-07-10 The Procter & Gamble Company Bismuth-containing pharmaceutical compositions

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PITLIK S.D. ET AL: "Cryptosporidial cholecystitis", N. ENGL. J. MED., 1983, 308/16 (967), USA, XP000602894 *
STEFFEN R.: "Worldwide efficacy of bismuth subsalicylate in the treatment of travelers' diarrhea", REV. INFECT. DIS., 1990, 12/SUPPL. 1 (S80-S86), USA, XP000602908 *
WITTNER M. ET AL: "Parasitic infections in AIDS patients: Cryptosporidiosis, isosporiasis, microsporidiosis, cyclosporiasis", INFECT. DIS. CLIN. NORTH AM., 1993, 7/3 (569-586), USA, XP000603005 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7300667B1 (en) 1999-05-27 2007-11-27 Euro-Celtique, S.A. Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract
US7364749B1 (en) 1999-05-27 2008-04-29 Euro-Celtique, S.A. Preparations for the application of anti-infective and/or anti-inflammatory agents

Also Published As

Publication number Publication date
CA2219771A1 (fr) 1996-11-14
JPH11504939A (ja) 1999-05-11
AU5733596A (en) 1996-11-29
EP0830134A1 (fr) 1998-03-25

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